(1) Field of Invention
The present invention relates to heart valves and vessels and, more particularly, to calcified polymeric valves and vessels having calcium appetite inclusions immersed therein.
(2) Description of Related Art
Valvular heart disease is the third-most common cause of heart problems in the United States. Aortic valve stenosis significantly affects a patient's quality of life once it is advanced (see the List of Incorporated Literature References, Literature Reference No. 1), and affects between two to percent of the elderly population, according to epidemiological studies (see Literature Reference No. 2). Calcification is by far the major cause of aortic valve stenosis (more than 80%), and among the affected patients, some have certain types of triggering congenital heart defects such as bicuspid valve or a history of rheumatic heart disease (see Literature Reference No. 1). Calcific aortic valve stenosis is a progressive disease, which is irreversible and can be fatal if left untreated. Pharmacological agents cannot currently prevent valvular calcification or help repair a damaged valve, since valve tissue is unable to spontaneously regenerate. Thus, aortic valve replacement/repair is the only current available treatment.
The introduction of transcatheter aortic valve replacement (TAVR) has revolutionized heart valve replacement procedures by offering minimally invasive treatment options for high-risk patients who have been considered unfit for traditional open-heart surgery. TAVR involves delivery, deployment, and implantation of a crimped, stented valve within the aortic annulus. A narrow range of FDA-approved transcatheter valves is currently being used in elderly patients with calcific aortic stenosis (see Literature Reference No. 3). Transcatheter aortic valves share similarities with bioprosthetic surgical heart valves, as both possess tissue leaflets. However, their major difference is the housing of the valves' leaflets within a stent. Contrary to the surgically-implantable aortic valves, transcatheter valves are not sewn within the aortic annulus but their stent expands within the native calcific aortic valve and the roughness due to the calcific nodules on the native leaflets provides means to hold the stented valve in place. The patterns of calcific nodules developed on the leaflets are completely random and vary in every patient.
Calcific aortic stenosis is mainly a disease of the human and has not ever been reported to naturally occur in animals. Very few attempts have been made to develop animal models with calcific aortic stenosis that were mainly mouse models (see Literature Reference Nos. 4-6), and no large animal model of calcific aortic stenosis is yet available. Lack of such an animal model makes the research and development studies related to prosthetic heart valves very difficult and costly. Most technologies related to transcatheter repair/replacement of aortic valve require a calcified heart valve in animals to show their feasibility. Currently, the preclinical studies related to TAVR have been performed on ovine or swine models with normal aortic valve (see Literature Reference Nos. 7-10). However, the experiments do not closely reflect the actual clinical situation, since these animals possess normal aortic valves without any trace of calcification. Therefore, not only a successful implant in sheep does not guarantee that the valve can similarly perform in a patient with calcific aortic valve but also a failed experiment due to lack of anchoring in the animal does not necessarily imply that the tested valve will fail in human with calcific aortic stenosis. Furthermore, since the calcific patterns in human aortic valve is remarkably heterogeneous, design and development of the TAVR systems suitable for most patients is extremely difficult due to the lack of a proper experimental model.
Thus, a continuing need exists for a valve whose leaflets possess calcium hydroxyapatite inclusions immersed in them and for valves that can be produced to replicate different grades of calcification (e.g., mild, moderate or severe) to test transcatheter aortic valve implantation in vitro or even in vivo. Such a calcified valve or vessel can be implanted in an experimental animal to have it prepared for a secondary device to be implanted therein to replicate a situation in a human that is considered a calsified or stenotic valve or vessel.